Tuesday, November 5, 2013

The Carbohydrate Monster Under your Bed Part 4

"Now one of Clinton’s Laws of Politics is this: If one candidate’s trying to scare you and the other one’s trying to get you to think; if one candidate’s appealing to your fears and the other one’s appealing to your hopes, you better vote for the person who wants you to think and hope. That’s the best."
– Bill Clinton, 2004

Appealing to a person's fear of the unknown or impending doom is an easy path to travel because it makes for a perfect vessel to transport self doubt and confusion into an individuals thoughts. This is done in order to harness someone elses belief system and turn it into trust and understanding for your own "Message" of salvation just over the other side of the hill....all for the convenient low price of $19.99. I'm of coarse referring to the various tactics that diet philosophies and propaganda use to scare the public into supporting their respective message about obesity, diabetes, weight loss, etc.

 In the previous section we covered De novo Lipogenesis and in this section we are going to examine the fate of fatty acids and their contribution to another delicate cycle in our body, The esterification and re-esterification of fatty acids.

 Re-esterification and Dietary fat 

The first process in the last section demonstrates the creating of new fat and storage from not fat precursors but what about the other process contributing to fatty acid homeostasis.

--> When we eat some food with fat in it, these are called dietary tricyleglycerols, the break down of which starts in the small intestines. IN the SI Bile salts from the gal bladder emulsify the insoluble dietary fats we just ate to form micelles.

--> The Micelles then continue down the small intestines where the enzyme Lipase , secreted from the pancreas, breaks down the triclylglycerols into fatty acids and glycerol.

--> The triclyglycerols are then packaged with apoproteins  ( specifically ApoB 48) and cholesterol to form blood soluble complexes called chylomicrons. Once formed into chylomicrons, they then move across the blood vessel membrane into the blood stream.

--> Once in the bloodstream, the chylomicrons have two fates. The Blood Borne Fats can travel to the fat to be stored in the fats cells or be oxidized for energy via beta oxidation ( see Part 2) in the muscle cells. 

--> For the storage of fat in adipocytes, the triacylglycerol is cleaved on the wall of the blood vessel by LPL or lipoprotein lipase into fatty acids and glycerol. These components then travel into the cells to be stored as triclyglycerols in fat droplets.

--> The fatty acids and glycerols are then released from the adipocytes when needed via Hormone sensitive lipase (HSL)

--> This happens when glucagon attaches itself to a G protein coupled receptor during times of low glucose oxidation when the body requires fuel.

--> The Alpha sub unit from the GPCR attaches itself to adenlyn Cyclase cuasing ATP to generate CAMP

--> CAMP then activates Protein Kinase A or PKA for short. This PKA will phosphorylate HSL, thus activating.

--> However, Before HSL can remove the Fatty acids from the lipid droplet, PKA must also phosphorylate the Perilipins which coat the lipid droplet.

--> HSL then brings the TAG out of the Lipid Droplet and turns them into G3P and Fatty acids.

--> The Fatty acids then tranfuse into the blood where they are picked up by serume albumin and taken where they need to go in the body. (i.e to the muscle or heart for beta oxidation or the liver to be turned into ketones or oxidized into ATP)

As the above graphic suggests many of the actions of fatty acid storage and release are regulated by the hormone Insulin which does the following:

+ Up regulates LPL activity

+ Translocates Glut-4 to the surface to shuttle in glucose

+ Facilitates Lipogenesis/conversion of glucose -> acetyl CoA --> Fatty acids

+ Facilitates the esterification processes (the combining of G3P and fatty acids to form TAG)

+ Inhibits HSL activity used for breakdown of TAG to FA and G3P

+ Acts on Malonyl - CoA which indirectly inhibits CPT1/ Basically stopping oxidation of Fatty Acids

All of the above makes sense as insulin is a signal of glucose abundance. Thus, signaling the stoppage of  the burning of fatty acid for fuel and to instead switch to the burning of glucose.

The above is a summary of what was discussed in Part 3 of this series but I bring this up because people often forget that dietary fat can be stored directly as Fat. Insulin is not required for the storage of fatty acids nor is it required to suppress the release of fatty acids via the suppression of HSL. See the below.

Little to No Insulin required for fat storage?

This study examines whether insulin is necessary for fat storage or not.

"The main aim of this study was to investigate the effects of oral ingestion of a pure fat load or infusion of the TAG emulsion Intralipid on LPL and HSL action and the fate of LPL-derived fatty acids in vivo in the absence of an insulin response." (40)

Six subjects between the ages of 26-44 and were not hyperglycemic or hyperlipidemic. The Subjects then received the following:

"On one occasion, the subjects received a 40-g fat load with only a small amount of carbohydrate in the form of tomato soup (Table1). On the other occasion, they received an intravenous infusion of Intralipid at a constant rate over 4 h to provide the same fat load. Blood samples were taken 40, 80, 120, 180, 240, 300, and 360 min after the soup or start of the infusion. Additional arterialized samples were taken at 20 and 60 min for glucose and insulin measurement only."(40)


"Glucose concentrations were slightly higher after the oral fat load, and this persisted throughout the study (Fig.2 A). Insulin concentrations showed a very small rise to peak at 8.9 mU/l at 60 min after the oral fat load and a gradual decrease in concentration during and after the infusion (Fig.2B)."(40)

"With both the oral and intravenous fat loads, there was a fall in HSL action in adipose tissue to close to zero after 3–4 h, followed by an increase back to baseline (Fig. 8). There was no significant difference in HSL action between the oral and intravenous fat loads."(40)

"The most striking feature of this study is the down regulation of HSL action during infusion of Intralipid. This down regulation is also seen after a mixed meal, when there is increased insulin action and increased re-esterification of fatty acids in adipose tissue. In our study, down regulation of HSL action occurred in the absence of increased insulin action and without fatty acid re-esterification in adipose tissue."(40)

"It seems that suppression of HSL activity can occur without insulin. Catecholamines are important in controlling HSL action. There is evidence that α2-adrenoceptor activation is strongly antilipolytic (16) and may account for the suppression of HSL activity without increased insulin action seen in this study. Alternatively, it may be that the fatty acids produced by LPL-mediated hydrolysis of chylomicrons or Intralipid particles caused suppression of HSL activity. There is some evidence, at least in cell-free systems, that fatty acids and their coenzyme A esters can inhibit HSL activity (23)"(40)

"These results suggest that insulin is not essential for HSL suppression or LPL activation in the postprandial period but may be important in reesterification of NEFA in adipose tissue, thus affecting NEFA partitioning between adipose tissue and the circulation."

This study also had similar findings:

Objective: "To test the hypothesis that intravenous infusion of lipid would bring about changes in adipose tissue metabolism, which would tend to spare net fat mobilization, and to attempt to identify the mediators of such responses."

Results: Plasma TG and non-esterified fatty acid (NEFA) concentrations rose during infusion as expected. The rise in systemic plasma NEFA concentration occurred despite decreased NEFA release from adipose tissue. Intralipid infusion resulted in a suppression of intracellular lipolysis in adipose tissue, by mechanisms which are not clear. Plasma leptin concentrations, measured in a search for the regulator of lipolysis, showed consistent leptin release from adipose tissue which did not change significantly with time.

Conclusion: "The suppression of intracellular lipolysis in adipose tissue during Intralipid infusion is a new observation and may reflect a novel mechanism for regulation of fat storage."

Lets go ahead and summarize what we just discussed in the last discussions in reference to the original equation:

Fat Stored - Fat Oxidized = Fatty acid Balance (+/-)

Fat can be stored by either:

1) Fatty acids being directly stored as fat
2) or by the conversion of non-fat precursors to fatty acids.

Fat is oxidized primarily through beta Oxidation which can be increased via exercise.

Oxidation of Fatty acids can be decreased by:

1) Increased levels of insulin/glucose in the blood
2) Increased level of chylomicrons in the blood

Let say as an example that a person eats 700 calories of carbohydrates, insulin will guide the glucose where it needs to go to be oxidized and will in turn suppress fatty acid release so the fatty acids do not interfere with the oxidation of Glucose.

Now lets say that instead of eating 700 calories of Carbohydrate, that person instead eats 700 calories of Fat. In this scenario, your body will instead use fat as a source of fuel and will stop fatty acid release because you do not need to dip into your fat stores.

Either way, the amount of carbon entering your body from either fat or carbohydrate with the same amount of calories will stop fatty acid release during feeding and will resume once feeding has concluded. The ultimate factor for maintaining proper fat balance is calories regardless of the source. 

To break it down in layman's terms:

Stop worrying about Insulin Spiking Fat Inducing Carbohydrates. Excessive fat consumption can make a person fat via direct storage if they are over consuming calories beyond their metabolic needs. 

This will become more apparent as this series goes on. So please open your eyes...

For Part 5 Click Here

To start from the beginning click Here